Radiation Oncology/Medulloblastoma/Overview

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Medulloblastoma Overview


Epidemiology[edit]

  • Most common malignant brain tumor of childhood (20% of CNS tumors in children <19 years old; glioma #1). 550 cases in the US
  • Median age of presentation is 5-7 years old. 75% medulloblastomas occur in children <15 years old.
  • Slight male predominance.
  • Highest risk of CSF+ at presentation (30-35%)

Clinical Presentation[edit]

  • Increased intracranial pressure: Headaches, nausea, vomiting
  • Cranial nerve deficits
  • Ataxic gait
  • In infants: loss of milestones, increased head circumference, head tilt due to CN IV palsy
  • Clinical exam: papilledema, nystagmus, CN abnormalities (VI most common -> "setting sun" sign with downward gaze)
  • 50-75% have <3 months of symptoms; prolonged symptoms duration multiplies probability of favourable treatment outcome of basic disease


Radiographic[edit]

  • Plain films: often invisible
  • CT: hyperdense on unenhanced study, enhances with contrast, can appear homogenous
  • MRI: hyperintense on T1, heterogenous on T2, often compresses 4th ventricle
  • Get imaging before starting steroids
    • Pre-op MRI brain and spinal cord (post-op spine can give false positives)
    • Post-op MRI brain within 48 hours
  • Pre-op CSF before surgery if safe (no increased ICP), else 10-14 days after surgery to avoid false-positive findings from surgical debris
  • If advanced, metastatic work-up


Histology[edit]

  • "Small round blue cell"; classified as primitive neuroectodermal tumor (PNET)
  • Medulloblasts are derived from cerebellar granule cells (account for almost half of all neurons in CNS), through activation of Sonic Hedgehog Pathway, likely from external granluar layer of the cerebellum
  • Genetics: Loss of 17p, 10q, 16q, chromosome 11; excess of 17q, chromosome 7

Prognostic Factors[edit]

  • Molecular profiling risk stratification (PMID 21357776)
    • Excellent prognosis: Wnt pathway
    • Good prognosis: Hh pathway (Hedgehog)
    • Fair prognosis: all others
    • Poor prognosis: c-MYC amplification
  • Histological risk stratification
    • Histologically poor prognosis: Large-cell anaplastic (LCA) variant, diploid DNA, LOH 17p, p53 mutation and expression, low TrkC (tyrosine kinase that mediates neuronal differentiation; 4.8x risk of death), MYC mRNA (c-myc/MYCC) expression, HER2-neu positive (ErbB2+), HER2+/HER4+ coexpression
    • Histologically better prognosis: Desmoplastic variant, high TrkC expression, ErbB2-, β-catenin (beta-catenin) nucleopositivity
  • Historical risk stratification:
    • Clinically poor prognosis: Age <3 years, M2-4 disease, unresectable or subtotal resection (>1.5 cm2)
    • Clinically better prognosis: Age >5-7 years, M0 disease (no metastasis), tumor is not visible on the postoperative image

Anatomy[edit]

  • Posterior Fossa borders
    • Anterior: clivus and posterior clinoid
    • Posterior: calvarium
    • Superior: tentorium
    • Inferior: occipital bone
    • Lateral: portions of temporal, occipital, parietal bones


Natural History[edit]

  • Dissemination: CSF seeding, intracranial, subarachnoid space, mets outside CNS <5%
  • Most recurrences within two years, at the site of primary tumor (50%)
  • Medulloblastoma tends to follow Collins' law (see PMID 9213055), which defines the period of risk for recurrence as the patient's age at diagnosis + 9 months of gestation. According to Collin's law, if a patient has no evidence of recurrence within this time period, he is considered cured (e.g. a 3 year old with medulloblastoma is cured when his disease free interval reaches 3 years + 9 months). The premise is that if this tumor was present in utero, then gestation+age determines rate of growth for it to become clinically evident. Therefore, if there is residual disease after treatment, it should become clinically evident again within the same time-frame
  • 10-year survival for all stages: 40-50%
  • For today considerable part of survivors is living 20-25 years and more from the moment of primary treatment


Other Resources[edit]